Featured Discovery

Home > Featured Discovery > SJTU and MIT Joint Research Advances Artificial Design of Membrane Proteins

SJTU and MIT Joint Research Advances Artificial Design of Membrane Proteins

November 04, 2020      Author:

Recently, iScience, a journal affiliated to Cell, published on its website a research paper titled "Non-full-length Water-Soluble CXCR4QTY and CCR5QTY Chemokine Receptors: Implication for Overlooked Truncated but Functional Membrane Receptors". The paper is a result of cooperation between the teams led by Professor Xu Ping from School of Life Sciences and Biotechnology of SJTU and Professor Zhang Shuguang (member of U.S. National Academy of Inventors, advisory professor of SJTU) from MIT Media Laboratory. It marks another breakthrough in the study of artificial design of membrane proteins. The teams found that non-full-length immune receptor proteins also have physiological functions, which were once thought to have no biological function. This is a reasonable but unexpected discovery, which can bring a new vision for the research on signal transduction and metabolic regulation and provide a new opportunity for the development of drugs, bionic devices and new diagnosis and treatment methods. Dr. Qing Rui from MIT research team and researcher Tao Fei from School of Life Sciences and Biotechnology of SJTU are the co-first authors of the paper, and Prof. Zhang Shuguang and Dr. Qing Rui are the co-corresponding authors.

SUMMARY:

It was posited that functionalities of GPCRs require full-length sequences that are negated by residue deletions. Here we report that significantly truncated nfCCR5QTY and nfCXCR4QTY still bind native ligands. Receptor-ligand interactions were discovered from yeast 2-hybrid screening and confirmed by mating selection. Two nfCCR5QTY (SZ218a, SZ190b) and two nfCXCR4QTY (SZ158a, SZ146a) were expressed in E. coli. Synthesized receptors exhibited α-helical structures and bound respective ligands with reduced affinities. SZ190b and SZ158a were reconverted into non-QTY forms and expressed in HEK293T cells. Reconverted receptors localized on cell membranes and functioned as negative regulators for ligand-induced signaling when co-expressed with full-length receptors. CCR5-SZ190b individually can perform signaling at a reduced level with higher ligand concentration. Our findings provide insight into essential structural components for CCR5 and CXCR4 functionality, while raising the possibility that non-full-length receptors may be resulted from alternative splicing and that pseudo-genes in genomes may be present and functional in living organisms.

 

Author: School of Life Sciences and Biotechnology

Affiliation: School of Life Sciences and Biotechnology 

Translated by Ge Haoyu

Proofread by Xiao Yangning